Article
Biochemistry & Molecular Biology
Mostapha Ahmad, Margarita R. Rios-Anillo, Johan E. Acosta-Lopez, Martha L. Cervantes-Henriquez, Martha Martinez-Banfi, Wilmar Pineda-Alhucema, Pedro Puentes-Rozo, Cristian Sanchez-Barros, Andres Pinzon, Hardip R. Patel, Jorge I. Velez, Jose Luis Villarreal-Camacho, David A. Pineda, Mauricio Arcos-Burgos, Manuel Sanchez-Rojas
Summary: This study analyzed the genetic and molecular features of 291 participants, including 33 with Huntington's disease (HD). The study found that mosaicism increased with age, particularly for the secondary allele, in HD participants. The most common haplotype observed was 17/7_17/10.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Clinical Neurology
Assunta Ingannato, Silvia Bagnoli, Valentina Bessi, Camilla Ferrari, Salvatore Mazzeo, Sandro Sorbi, Benedetta Nacmias
Summary: This study investigates the role of HTT Intermediate alleles (IAs) in extreme longevity and their association with cognitive decline. The results show a higher frequency of IAs in Centenarians compared to pathological controls with cognitive decline, suggesting a possible implication of HTT gene in exceptional lifespan and brain development with a neuroprotective effect.
JOURNAL OF THE NEUROLOGICAL SCIENCES
(2022)
Article
Clinical Neurology
Erin I. McDonnell, Yuanjia Wang, Jill Goldman, Karen Marder
Summary: This study provides allele-specific estimates of HD penetrance for RP allele carriers with different CAG repeat lengths, with 37 repeats being unestimable. Although there were differences by RP-range repeat length, they did not reach significance during the 3-year median follow-up duration among censored individuals.
MOVEMENT DISORDERS
(2021)
Article
Neurosciences
Kathryn H. Morelli, Qian Wu, Maya L. Gosztyla, Hongshuai Liu, Minmin Yao, Chuangchuang Zhang, Jiaxu Chen, Ryan J. Marina, Kari Lee, Krysten L. Jones, Megan Y. Huang, Allison Li, Charlene Smith-Geater, Leslie M. Thompson, Wenzhen Duan, Gene W. Yeo
Summary: Huntington's disease is a neurodegenerative disorder caused by genetic mutation. Researchers have developed a CRISPR-Cas13d system to target and eliminate the mutant RNA responsible for the disease. In animal models, this approach successfully reduced mutant protein levels and improved motor coordination without adverse effects. This study provides proof of concept for RNA-targeting CRISPR-Cas13d system as a potential therapeutic approach for Huntington's disease.
NATURE NEUROSCIENCE
(2023)
Review
Biochemistry & Molecular Biology
Pratik Talukder, Annapurna Jana, Shrirupa Dhar, Saikat Ghosh
Summary: Huntington's disease is a neurodegenerative disorder caused by expansion of CAG repeats in the huntingtin gene. Phosphorylation of translation initiation factor 4E-BP can lead to abnormal protein synthesis and neuronal function. The variability in age of onset is influenced by genetic modifiers, maternal protection, superior aging genes, and environmental factors. Major focus is on the pathogenesis involving motor, cognitive, and neuropsychiatric disturbances, with diagnosis including genetic testing and symptom identification.
APPLIED BIOCHEMISTRY AND BIOTECHNOLOGY
(2021)
Article
Medicine, General & Internal
Moutushi Ahmed, Debasish Mridha
Summary: This study presents the clinical features and disease progression of a 39-year-old male patient diagnosed with Huntington's disease (HD). The diagnosis was confirmed by direct genetic testing, using DNA obtained from a blood sample that revealed expanded cytosine-adenine-guanine (CAG) repeats in the huntingtin gene (HD gene). The patient exhibited motor symptoms, cognitive symptoms, and experienced progressive deterioration that resulted in wheelchair dependency and increased reliance on supportive care.
CUREUS JOURNAL OF MEDICAL SCIENCE
(2023)
Editorial Material
Neurosciences
Hyeseung Lee, Myriam Heiman
Summary: In this study, the authors present a novel BAC mouse model that accurately recapitulates various aspects of Huntington's disease and provides important insights into the relative toxicities of mHTT-derived products.
Article
Clinical Neurology
Martina Petracca, Sonia Di Tella, Marcella Solito, Paola Zinzi, Maria Rita Lo Monaco, Giulia Di Lazzaro, Paolo Calabresi, Maria Caterina Silveri, Anna Rita Bentivoglio
Summary: Late-onset HD mainly presents as a motor-onset disease with lower prevalence of psychiatric history and current symptoms. The LoHD group has more severe motor and cognitive deficits compared to the HS group. Absent/unknown HD family history is more common in the LoHD group than in other groups.
EUROPEAN JOURNAL OF NEUROLOGY
(2022)
Article
Neurosciences
Assunta Ingannato, Silvia Bagnoli, Salvatore Mazzeo, Valentina Bessi, Sabrina Mata, Monica Del Mastio, Gemma Lombardi, Camilla Ferrari, Sandro Sorbi, Benedetta Nacmias
Summary: The study found that intermediate alleles and plasma NfL levels may potentially serve as biomarkers in ALS, with higher frequency of IAs in the patient cohort, increasing NfL levels with age at onset, and differences in NfL concentration and age at onset between bulbar and spinal onset groups.
FRONTIERS IN NEUROSCIENCE
(2021)
Article
Neurosciences
Dazhang Bai, Longhong Zhu, Qingqing Jia, Xuezhi Duan, Laiqiang Chen, Xiang Wang, Junqi Hou, Guohui Jiang, Su Yang, Shihua Li, Xiao-Jiang Li, Peng Yin
Summary: Loss of TDP-43 leads to expansion of CAG repeat in Huntington's disease gene by dysregulating the expression of DNA mismatch repair genes. These findings highlight the importance of TDP-43 in the pathogenesis of CAG repeat diseases.
PROGRESS IN NEUROBIOLOGY
(2023)
Article
Neurosciences
Maria Serpente, Chiara Fenoglio, Andrea Arighi, Giorgio G. Fumagalli, Marina Arcaro, Federica Sorrentino, Caterina Visconte, Elio Scarpini, Daniela Galimberti
Summary: The study found a significant increase in the frequency of C9orf72 intermediate repeat alleles in patients with Alzheimer's disease, but no significant differences were observed in other dementia patients compared to non-demented individuals. This suggests that C9orf72 intermediate repeat units may be a genetic risk factor for the occurrence of Alzheimer's disease.
JOURNAL OF ALZHEIMERS DISEASE
(2021)
Article
Neurosciences
Nikhil Ratna, Swathi Lakshmi Pasupulati, Ravi K. Nadella, Meera Purushottam, Sanjeev Jain
Summary: The complex inheritance patterns of Huntington's Disease pose challenges for genetic counseling and testing, highlighting the importance of proper counseling for better outcomes.
Article
Biochemistry & Molecular Biology
Adam Ciesiolka, Anna Stroynowska-Czerwinska, Pawel Joachimiak, Agata Ciolak, Emilia Kozlowska, Michal Michalak, Magdalena Dabrowska, Marta Olejniczak, Katarzyna D. Raczynska, Dominika Zielinska, Magdalena Wozna-Wysocka, Wlodzimierz J. Krzyzosiak, Agnieszka Fiszer
Summary: Polyglutamine diseases, such as Huntington's disease, are incurable neurological disorders caused by CAG repeat expansion in specific genes. The use of CAG repeat-targeting artificial miRNAs shows promise in selectively decreasing mutant protein levels. Research suggests that the efficiency and selectivity of art-miRNAs are influenced by the localization and sequence context of CAG repeats in the transcript. Additionally, the downregulation of mutant polyQ proteins involves rapid activation of translational repression and transcript deadenylation, with the slicer activity of AGO2 being dispensable in this process.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2021)
Article
Genetics & Heredity
Yu-Feng Bao, Xiao-Yan Li, Yi Dong, Zhi-Ying Wu
Summary: This study identifies LOI variants in Chinese HD patients for the first time and suggests that HTT gene sequencing should be considered for symptomatic individuals with intermediate or reduced penetrance allele, or negative family history.
JOURNAL OF MOLECULAR MEDICINE-JMM
(2023)
Article
Clinical Neurology
Miguel angel Ramirez-Garcia, David Jose Dvila-Ortiz de Montellano, Leticia Martinez-Ruano, Adriana Ochoa-Morales, Sandra Romero-Hidalgo, Juan Carlos Zenteno, Petra Yescas-Gomez
Summary: This study describes the general and clinical features of a case series with IA carriers and excludes HD phenocopies through molecular assessment. The results show a high proportion of manifestations of the HD phenotypic spectrum in the IA-non-HD subgroup, and also identify HDL2 and choreoacanthocytosis cases.
NEURODEGENERATIVE DISEASES
(2022)
Correction
Clinical Neurology
Saul Martinez-Horta, Andrea Horta-Barba, Jesus Perez-Perez, Frederic Sampedro, Natascia de Lucia, Giuseppe De Michele, Stefanie Kehrer, Josef Priller, Simone Migliore, Ferdinando Squitieri, Anna Castaldo, Caterina Mariotti, Veronica Mananes, Jose Luis Lopez-Sendon, Noelia Rodriguez, Asuncion Martinez-Descals, Pedro Garcia-Ruiz, Filipa Julio, Cristina Januario, Marianna Delussi, Marina de Tommaso, Sandra Noguera, Jesus Ruiz-Idiago, Emilia J. Sitek, Angela Nuzzi, Javier Pagonabarraga, Jaime Kulisevsky
JOURNAL OF NEUROLOGY
(2021)
Article
Biochemistry & Molecular Biology
Theo Battista, Gianmarco Pascarella, David Sasah Staid, Gianni Colotti, Jessica Rosati, Annarita Fiorillo, Alessia Casamassa, Angelo Luigi Vescovi, Barbara Giabbai, Marta Stefania Semrau, Sergio Fanelli, Paola Storici, Ferdinando Squitieri, Veronica Morea, Andrea Ilari
Summary: The study utilized a drug repositioning strategy to identify six drugs that can directly bind sigma 1R and improve the growth of cells from Huntington disease patients. These drugs have shown efficacy in providing new therapeutic tools against HD, offering hope for future treatments.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Alessandro De Luca, Annunziata Morella, Federica Consoli, Sergio Fanelli, Julie R. Thibert, Sarah Statt, Gary J. Latham, Ferdinando Squitieri
Summary: The study demonstrates that the AmplideX PCR/CE HTT Kit technology can accurately detect the expansion of CAG repeat sequences in the HTT gene, including large and very large expansions, thereby improving the reliability and accuracy of genetic testing.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Correction
Clinical Neurology
Simone Migliore, Doriana Landi, Francesca Proietti, Giulia D'Aurizio, Ferdinando Squitieri, Giorgia Mataluni, Carolina Gabri Nicoletti, Giuseppe Curcio, Girolama Alessandra Marfia
NEUROLOGICAL SCIENCES
(2021)
Article
Clinical Neurology
Simone Migliore, Doriana Landi, Francesca Proietti, Giulia D'Aurizio, Ferdinando Squitieri, Giorgia Mataluni, Carolina Gabri Nicoletti, Giuseppe Curcio, GirolamaAlessandraAlessandra Alessandra Marfia
Summary: The study validated the Italian version of the Multiple Sclerosis Neuropsychological Questionnaire (MSNQ) and found correlations between MSNQ scores and cognitive skills, mood status, and physical disability, highlighting its reliability as a screening tool for identifying MS patients at high risk of cognitive impairment.
NEUROLOGICAL SCIENCES
(2021)
Article
Clinical Neurology
Laura Carelli, Federica Solca, Simone Migliore, Silvia Torre, Agostino Brugnera, Francesca Mancini, Sofia Tagini, Roberta Ferrucci, Sabrina Maffi, Consuelo Ceccarelli, Jacopo Pasquini, Jenny Sassone, Ferdinando Squitieri, Andrea Ciammola, Vincenzo Silani, Barbara Poletti
Summary: The ECAS can effectively differentiate between HD patients and HC, as well as the two clinical syndromes, with high sensitivity and specificity. Although the diagnostic accuracy of the ECAS in distinguishing between PD and HC is low, it provides a good description of the PD cognitive phenotype. The ECAS also shows convergent validity with other traditional cognitive screening tools, and correlations with psychological aspects and typical clinical features, especially in the HD group.
NEUROLOGICAL SCIENCES
(2021)
Article
Behavioral Sciences
Simone Migliore, Giulia D'Aurizio, Sabrina Maffi, Consuelo Ceccarelli, Giovanni Ristori, Silvia Romano, Anna Castaldo, Caterina Mariotti, Giuseppe Curcio, Ferdinando Squitieri
Summary: The study showed a significant association between cognitive decline and severity of apathy and perseveration/obsessions in Huntington disease (HD) patients, with disease progression confirmed after two years. This suggests an important role of cognitive and behavioral changes in the development of HD.
BRAIN AND BEHAVIOR
(2021)
Article
Clinical Neurology
Pearl J. C. van Lonkhuizen, Niko J. H. Vegt, Eline Meijer, Erik van Duijn, Susanne T. de Bot, Jiri Klempir, Wiebke Frank, G. Bernhard Landwehrmeyer, Alzbeta Muehlbaeck, Jennifer Hoblyn, Ferdinando Squitieri, Peter Foley, Niels H. Chavannes, Anne-Wil Heemskerk
Summary: The study aims to develop a multinational eHealth platform targeting the needs of HDGECs and their partners, involving end-users in all design decisions to provide high-quality, tailored care and testing the platform in different healthcare systems and cultural contexts.
FRONTIERS IN NEUROLOGY
(2021)
Article
Health Care Sciences & Services
Filipa Julio, Ruth Blanco, Jose Perez Casanova, Barbara D'Alessio, Beatrice De Schepper, Dina De Sousa, Paul De Sousa, Cristina Ferreira, Hans Gommans, Rob Haselberg, Emilie Hermant, Danuta Lis, Sabrina Maffi, Svein Olaf Olsen, Marios Papantoniou, Ferdinando Squitieri, Marina Tretyakova, Zaynab Umakhanova, Vladimir Vaclavik, Michaela Winkelmann, Astri Arnesen
Summary: Progress has been made in Huntington's disease research, but effective treatments before disabling symptoms are still lacking. The European Huntington Association surveyed individuals at risk and with premanifest HD to determine factors affecting their willingness to participate in research. Motivation to participate in research is high, influenced by subjective and objective factors, HD status, and the role of patient organizations in fostering motivation through education and support.
JOURNAL OF PERSONALIZED MEDICINE
(2021)
Article
Health Care Sciences & Services
Federica Graziola, Sabrina Maffi, Melissa Grasso, Giacomo Garone, Simone Migliore, Eugenia Scaricamazza, Consuelo Ceccarelli, Melissa Casella, Ludovica Busi, Barbara D'Alessio, Alessandro De Luca, Giovanna Stefania Colafati, Umberto Sabatini, Alessandro Capuano, Ferdinando Squitieri
Summary: The Spazio Huntington program aims to study pediatric Huntington disease (PHD) by providing counseling, evaluating motor, cognitive, and behavioral changes, and conducting follow-ups. Magnetic resonance imaging can confirm initial abnormalities in PHD. This program may serve as a basis for recruiting PHD patients in future clinical trials.
JOURNAL OF PERSONALIZED MEDICINE
(2022)
Article
Health Care Sciences & Services
Simone Migliore, Giulia D'Aurizio, Eugenia Scaricamazza, Sabrina Maffi, Consuelo Ceccarelli, Giovanni Ristori, Silvia Romano, Anna Castaldo, Mario Fichera, Giuseppe Curcio, Ferdinando Squitieri
Summary: This study focused on Cognitive Reserve (CR) in patients with early Huntington Disease (HD) and found that lifetime intellectual enrichment may influence clinical outcomes. The results indicated that leisure time cognitive reserve was inversely associated with functional impairment and HD progression, while positively associated with cognitive performance.
JOURNAL OF PERSONALIZED MEDICINE
(2022)
Article
Neurosciences
Andrea Horta-Barba, Saul Martinez-Horta, Jesus Perez-Perez, Frederic Sampedro, Natascia de Lucia, Giuseppe De Michele, Elena Salvatore, Stefanie Kehrer, Josef Priller, Simone Migliore, Ferdinando Squitieri, Anna Castaldo, Caterina Mariotti, Veronica Mananes, Jose Luis Lopez-Sendon, Noelia Rodriguez, Asuncion Martinez-Descals, Filipa Julio, Cristina Janurio, Marianna Delussi, Marina de Tommaso, Sandra Noguera, Jesus Ruiz-Idiago, Emilia J. Sitek, Renata Wallner, Angela Nuzzi, Javier Pagonabarraga, Jaime Kulisevsky
Summary: This study aimed to investigate the performance of arithmetic tasks in Huntington's disease (HD) patients, and found that arithmetic word-problem solving is affected early in the course of the disease, and is related to deficient processes in frontal-executive and mentalizing-related processes.
JOURNAL OF HUNTINGTONS DISEASE
(2021)
Article
Health Care Sciences & Services
Sabrina Maffi, Eugenia Scaricamazza, Simone Migliore, Melissa Casella, Consuelo Ceccarelli, Ferdinando Squitieri
Summary: This study investigated the correlations between sleep features and motor, cognitive, behavioral, and functional changes in individuals with Huntington's disease (HD). The results showed a significant association between sleep abnormalities and the severity of disease progression, as well as impaired independence, cognitive performance, and motor functions. Sleep abnormalities are an important aspect of the clinical profile of HD and can greatly impact patients' quality of life.
JOURNAL OF PERSONALIZED MEDICINE
(2022)
Article
Public, Environmental & Occupational Health
Valerie Crowell, Richard Houghton, Akanksha Tomar, Tricia Fernandes, Ferdinando Squitieri
Summary: Understanding the epidemiology of Huntington's disease is crucial for assessing disease burden and healthcare resource allocation. A model was developed and validated to estimate the diagnosed prevalence of the disease, with data from 8 countries indicating an estimated 66,787 individuals diagnosed with HD in 2020. The majority of patients were in less severe stages, with diagnosed prevalence rates varying between countries.
Article
Neurosciences
Marta Olivetti Belardinelli, Thomas Hunefeldt, Roberta Meloni, Ferdinando Squitieri, Sabrina Maffi, Simone Migliore
Summary: Huntington's disease is a genetic neurodegenerative disorder that affects motor, cognitive, and neuropsychiatric functions. Research shows that deficits in mental state recognition may appear in early pre-manifest stages of the disease, and are related to abnormalities in visual scanning behavior.
EXPERIMENTAL BRAIN RESEARCH
(2021)